Fungal infections are the major problem in the treatment of immuno-compromised patients and those suffering from AIDS. The current antifungal agents belong to various groups like polyenes, allylamines, antimetabolites, azoles, glucan synthesis inhibitors etc. Fluconazole is a member of the family of azole antifungals. Fluconazole is orally active and has low toxicity but its extensive use has resulted in emergence of fluconazole-resistant fungal strains. Therefore, it is necessary to meet the long-felt need to develop novel fluconazole analogues which exert high anti-fungal activity against various fungi including Candida albicans, Aspergillus niger and Fusarium proliferatum with MIC values 2 to 8 fold lower than that of fluconazole.
The presence of one triazole ring, halogenated phenyl ring and tertiary alcoholic oxygen functionality in fluconazole is necessary for activity. The present invention seeks to provide novel azoles and process thereof as an effort to come up with antifungal agents with broad spectrum of antifungal activity. Fluconazole analogues have been reported having antifungal activity in the literature.
A series of fluconazole analogues incorporating azaindole and indole moieties were described in “Synthesis and anti-fungal activities of new fluconazole analogues with azoheterocycle moiety”, Bioorg Med Chem Lett 2007 Jul. 1; 17(13), 3686-9.